The major objective of this proposal is to explore a series of novel synthetic reactions which culminate in new synthetic routes to pharmaceutically-important aromatic and heteroaromatic compounds, including synthetic steroids, etoposide anti-cancer drugs, and 2-arylfuran natural products. The reaction under investigation involves the coupling of highly conjugated acetylene derivatives with Fischer carbene complexes, and is divided into two sections: coupling of carbene complexes with enzyme-carbonyl compounds, and coupling complexes with conjugated enediynes. The major focus involves exploration of the coupling of Fischer carbene complexes with enyne-carbonyl compounds, which provides the biologically-important furan ring system in a single step. Extension of the reaction to aromatic systems will lead to the unstable isobenzofuran ring system, which can undergo high-yielding a predictable reactions with electron-deficient alkenes. Exploitation of this reaction for the single step synthesis of the steroid ring system provides a remarkable versatile method to prepare a diverse array of steroid derivatives for biological testing. A similar reaction process can provide rapid synthetic routs to the structural analogs of the anti-cancer drug etoposide. The other area to be investigated is the coupling of conjugated enediynes with Fischer carbene complexes. This reaction process affords aromatic diradical intermediates, and a major effort will be made to understand and control the reaction pathways of the free radical intermediates. A major feature of these reaction processes is the selective introduction of functional groups into unfunctionalized alkyl chains. Use of this reaction for the synthesis of 2-arylfuran natural products will also be investigated. The field of synthetic organic chemistry has had a profound impact on human health. Investigation of the synthesis of pharmaceutically- important molecules can provide analogs, which are useful for maximizing the desired pharmacological effects and for a better understanding of the mode of action.